TRALI is a common clinical complication of transfusion. It is the leading cause of transfusion-related death in the United States. TRALI usually develops within 6 hours of transfusion. However, it can be observed within 1˜2 hours after transfusion. Symptoms of TRALI consist of the rapid onset of tachypnea, cyanosis, dyspnea, and fever. TRALI syndrome is difficult to diagnose, because initially it shares similar symptoms with transfusion-independent lung insufficiency (ALI) or ARDS (“acquired respiratory distress syndrome”) (Popovsky & Moore, Transfusion 25:573-577, 1985). TRALI is often misdiagnosed in the clinic because the symptoms are attributed to fluid overload. TRALI has been associated with the transfusions of all plasma related components, including whole blood, red blood concentrates, fresh frozen plasma, whole blood derived from platelets, pooled platelets, intravenous gamma-globulin, cryoprecipitate, stem cells and granulocytes. Because TRALI affects the pulmonary microvascular tissue, treatment focuses on respiratory support and saline infusion. The mortality rate from TRALI ranges from 5% to 25%. In North America, a case of TRALI happens 1 per 5,000 to 1 per 1,323 transfusions. Most patients recover within 72 hours; however, data for TRALI are limited, and the reported morbidity and mortality rate may be underestimated because of lack of recognition and underreporting.
TRALI is primarily associated with antibodies specific for HNA, granulocyte- and human leukocyte antigens (HLA) Class I and Class II. Other factors known to induce TRALI in transfusion recipients include biologically active lipids. In most cases, antibodies of the donor (in the donor plasma) react with the leucocytes (granulocytes) of the recipient. Binding of antibodies to the granulocytes activates the granulocytes and leads to aggregation. Oxygen radicals, cytokines, and proteases are released from the complement-activated granulocytes, damaging the capillary endothelium and causing. Extravasation of protein-rich fluid into the pulmonary alveoli and interstitium. In addition, the donor antibodies also bind to and activate granulocytes, of the recipient, and stimulate the expression of adhesion molecules (Uchiyama et al. Transfus. Med. Rev. 8:84-95, 1994). The immunological response also causes transmigration of granulocytes into the interstitial space between alveolar and vessel endothelium of the lung. (Snyder, Immol Invest. 24:333-9, 1994). These cellular effects cause damage to the capillary walls with subsequent hyperpermeability. A lung edema develops and 10% of the affected patients die from this complication.
A high percentage of TRALI cases are caused by blood donated by females, particularly multiparous women, because pregnant women can develop antibodies against granulocyte- or HLA-antigens of the child. A patient may be also immunized as the result of an earlier transfusion (Voss et al., Anaesthesist 50:930-932, 2001). Proposed current solutions for reducing the incidence of TRALI include the exclusion of all female donors, or at least the exclusion of multiparous (three or more pregnancies) female donors, and/or reducing the transfusion of fresh, frozen plasma.
Most blood and tissue donors have not been typed for HNA. Currently, the detection of granulocyte-specific antibodies is laborious; and detection of HNA antibodies in the serum of the blood donor is not sufficient. The requirement for lab technicians specialized in the nature of neutrophils, the lack of available HNA typing sera and the need to provide fresh neutrophils make typing HNA on a larger scale impractical, if not impossible, for most laboratories. Currently, the most reliable determination of TRALI risk is cross-matching between donor serum and patient leucocytes. This test can be carried out only in specialized laboratories (Voss, Anaesthesist 50:930-932, 2001) which are not suitable for donor screening. Other strategies include donor restriction management (Mair et al., Crit. Care Med. 34:137-143, 2006), causing significant reduction in the amount of stored blood because it excludes women from blood donation after pregnancy.
There is a need for more sensitive methods of detecting HNA specific antibodies in biological samples which will assist in predicting the risk of the transfusion or transplant recipient developing TRALI.